To examine the effect of vasopressin on the sarcolemmal ATP-sensitive K (K(ATP)) channel, cell-attached, insideout and open-cell-attached methods of patch clamp techniques were used in isolated guinea pig ventricular myocytes. Suppressing both glycolytic and oxidative ATP production attained K(ATP) channel activation. In the cell-attached mode, vasopressin inhibited KATP channels in a concentration-dependent manner with an IC50 of 15.1+/-1.8 nmol/L. In the inside-out configuration, vasopressin failed to block K(ATP) channels. In the cell-attached mode, manning compound (1 micromol/L), a V1 receptor-selective antagonist, blocked the inhibitory action of vasopressin, although OPC-31260 (1 micromol/L), a V2 receptor-selective antagonist could not affect the action of vasopressin. In addition, vasopressin lost its inhibitory action on K(ATP) channels when the channel was activated by pinacidil, a K channel opener and in the open-cell-attached mode effected by streptolysin-O. Thus, the inhibitory action of vasopressin K(ATP) channels may occur via V1 receptor related mechanism.